A History of Genetic Fingerprinting at the University of Leicester
[includes Profile of Professor Sir Alec Jeffreys and thumbnail sketch of his
discovery]

THE MAN WHO PUT THE FINGERPRINT
IN GENETICS

You could say that the path that led to the
discovery of genetic fingerprinting began for Professor Sir Alec Jeffreys when
his father gave him a chemistry set and a microscope at the age of eight.

Scientists, he believes, like musicians are
born not made, nonetheless he acknowledges that this parental encouragement
played its part in his choice of vocation. It might have been disastrous, as
he explained. “This was a real chemist’s chemistry set, not a child’s
toy, and later, when I was 13 or 14, I got a face full of sulphuric acid,
which is why I wear this beard now. I consider it a badge of honour.”

At Oxford the young Alec Jeffreys did a
four-year biochemistry degree before deciding that biochemistry was not for
him. His real enthusiasm had been for the genetic component of his degree
course, though looking back now he calls it “human genetics of the stone age
era”.

As a postdoctoral research fellow at the
University of Amsterdam, his original plan was to work with yeast. “Then I
met Dick Flavell and we started to work with mammalian genes. We didn’t
succeed in our original aims but we did develop a method for detecting
specific genes in humans. It was crude but it gave us a glimpse into what
human genes look like. We stumbled on the fact that mammalian genes look
weird, they are not simple as in bacteria. They have gaps, so that in between
the information sections of the genes were stretches of gobbledegook. Similar
research led to a Nobel Prize for other teams working in the field, so you can
see we were right in the centre of things.”

Just as his two years in Amsterdam were up,
while he was trying to decide between a second post doctoral term and an
independent academic position, he received a phone call from Professor Bob
Pritchard inviting him for interview for a temporary lecturership at
Leicester.

Speaking of the impression the University made
on him, he said: “I liked it. Remember I had spent seven years at Oxford,
where there is a collegiate system and less sense of a university. In
Amsterdam I had worked in a research institute, which was prestigious but also
had a different atmosphere. I liked the compact integrated campus at
Leicester. The department was friendly, there was no obvious sense of power
politics. Bob Pritchard made it clear I should just get on and do my research
without interference from him, and I liked that.”

Back in 1977 Leicester, the new recruit to the
University, aged just 27, in charge of a small laboratory and with one
part-time technician, had considerable freedom. The technology now existed for
the first time to look at genes, and he decided to study their inherited
variation, shifting the focus from the products of genes such as blood groups,
to DNA.

Those must have been exciting times in the
genetics laboratory. “That year we found the first inherited DNA variation
in one of our technicians. In 1978 we discovered you could detect variations
in human DNA. Then we worked on mapping genes in disease diagnosis. By 1981 we
could define our goal, which was highly variable DNA. We considered a number
of approaches which didn’t work, before looking at how genetic variations
evolved. We stumbled on our clue, stuttered DNA, or ‘minisatellites’,
which were highly variable. We had found a way of detecting lots of
minisatellites variable enough to provide extremely informative genetic
markers.

“My life changed on Monday morning at 9.05
am, 10 September 1984. What emerged was the world’s first genetic
fingerprint. In science it is unusual to have such a ‘eureka’ moment. We
were getting extraordinarily variable patterns of DNA, including from our
technician and her mother and father, as well as from non human samples. My
first reaction to the results was ‘this is too complicated’, and then the
penny dropped and I realised we had genetic fingerprinting.”

It opened up a new area of science. The
research team immediately grasped its applications, including crime, paternity
and identical twins, as well as work on conservation and diversity among
non-human species. Later that day Sir Alec’s wife added another to the list
- immigration. “That was when I realised this had a political dimension and
that it could change the face of immigration disputes, especially where no
documentary evidence existed.”

The first “real” immigration case came in
March 1985, a decade earlier than Sir Alec had anticipated, driven by the
demand from families and lawyers. “We even had people coming into our back
garden, asking to be tested there and then, which of course I couldn’t do,
not being a licensed blood taker. If our first case had been forensic I
believe it would have been challenged and the process may well have been
damaged in the courts. But our first application was to save a young boy and
it captured the public’s sympathy and imagination. It was science helping an
individual challenge authority. Of all the cases this is the one that means
most to me. The court allowed me to let the family know we had proved their
case, and I shall never forget the look in the mother’s eyes.”

The first paternity case came hot on the heels
of that dispute and then - in Sir Alec’s words - “the flood gates opened”.
At this point, all cases were dealt with by the Leicester laboratory. Sir Alec
was a research fellow for the Lister Institute who gave him funding to take on
another technician to enable them to run tests on a larger scale and for two
years his was the only laboratory in the world doing this work. He describes
it as “exciting but exhausting”, and had no regrets when ICI (now
AstraZeneca) were granted a licence to set up Cellmark and put the research on
a commercial level.

At this time the forensic implications of
genetic fingerprinting were emerging. The original process proved to be
inadequate for this, and so from 1985 Sir Alec and his team developed a
variation which they called “genetic profiling” for forensic use.

Again, its first application caught the public
mood. Two young girls were raped and murdered in the Enderby area of
Leicestershire. A man who had been arrested had confessed to one murder but
not the other, and the police decided to use genetic profiling, thinking to
prove him guilty of both cases. Against all expectation he was found to be
innocent of both. Then the hunt was on to find a genetic profile among the
entire male population of the area that matched samples taken from the two
victims. No match was found, until Colin Pitchfork was overheard boasting of
how he had persuaded a friend to give a sample on his behalf. The case was
solved.

How did Sir Alec feel when Pitchfork was
finally convicted? “I felt relief because he was a serial murderer and would
kill again, and because if the operation had failed then the public’s
perception of forensic DNA would have been shattered. Also, here was a serial
killer in the region who knew what I was doing and where I worked and where my
family lived. That feels very uncomfortable so on a personal level it was a
great relief when he was trapped.”

The original technology used to catch Pitchfork
is now largely obsolete, though still in use in some laboratories around the
world. But the techniques have been speeded up and simplified. In the UK we
now have a national database of 2.5 million genetic profiles from convicted
criminals which the police say is one of the most powerful tools in their
fight against crime. While there is some concern amongst civil rights
activists, Sir Alec feels it would be “criminally irresponsible” not to
maintain the database and would mean that rapists and murderers who are now
identifiable would be able to continue unstopped. However, he does take civil
rights seriously and is concerned with the fact that suspects’ DNA profiles
are also being stored on police records. He sees this as discriminatory,
though notes that this potential infringement of civil rights of minority
groups would largely disappear if everybody was ‘fingerprinted’.

“Where it is a matter of identification of
genetic disease I feel insurance companies and their like have no right to
genetic information. This is private property and no one other than the
individual concerned should have that information. We all carry within us the
equivalent of three lethal genetic variants, so why should insurance companies
have access to information on selected cases? The information should only be
used if it helps the individual, for instance if there is a treatment for the
disease.”

Not all Sir Alec’s cases have been so intense
nor with such portentous implications. In the early 1990s he received a phone
call from the producer of BBC Television’s “Jim’ll fix It”. There were
twins, 11-year-old girls, who wanted to know if they were identical or not.
Could he help? Since identical twins are the only people who share genetic
fingerprints, Sir Alec could certainly help. “Cellmark Diagnostics leapt on
this, it was fun. Once we had the results we went down to the studio, set up
the DNA fingerprints behind a curtain and invited the girls to draw the
curtain. They saw for themselves that they were identical. Then I had the
opportunity to explain the scientific processes to an audience of 20 million
people.”

BEYOND GENETIC FINGERPRINTING

Since the late 1980s Professor Sir Alec
Jeffreys has been examining the ways DNA mutates and crosses over (reshuffles
its chromosomes), looking at minisatellites and the spontaneous ways in which
they add and lose stutters.

With Professor Yuri Dubrova from the NI Vavilov
Institute of General Genetics, Moscow, he has studied 79 familes in the region
around Chernobyl in Belarus, the scene of the 1986 nuclear accident, to find
out whether the environment we live in influences this mutation, or whether it
all comes from our genes.

The research concentrates on three groups of
people who have been exposed to radiation:

Those exposed by accident, such as survivors
of the Chernobyl disaster or the bombing of Hiroshima and Nagasaki;

Those deliberately exposed in the sense they
live near nuclear test weapon sites;

Those deliberately exposed, for example in
the treatment of cancers.

Results so far have been perplexing. In the
Chernobyl region the genetic mutation rate was found to be unusually high. In
other words parents in that area pass on mutations to their children more than
elsewhere. But it is impossible to point the finger of accusation at radiation
alone. For instance, the population of Belarus is more stressed than in
non-contaminated environments, and people’s health may be affected by
stress-related behaviour like smoking. However, those living near nuclear
weapon test sites also show increased levels of heritable mutation, suggesting
a direct effect of radiation. On the other hand sperm from men undergoing
radiation for cancer treatment shows no change in genetic mutation at all, nor
do samples from the remaining survivors of Hiroshima and Nagasaki.

Questions to be explored include whether
Chernobyl families living in more contaminated areas show more genetic
mutation than those in clearer districts, or whether the way people receive
the radiation is significant, i.e. from a single bomb blast as opposed to
living in a contaminated environment and consuming radioactive material in
food and drink.

It is a project that will, Sir Alec foresees,
take him to retirement. For a scientist who enjoys venturing into the unknown
he seems well content to take up the challenge.

DNA - A THUMBNAIL SKETCH

DNA is deoxyribonucleic acid, the molecules
in cells that determine the genetic characteristics of all life. It takes
the form of a double helix (two strands coiled together).

DNA was first discovered in the 19th century
by Miescher, from pus on bandages.

By the 1940s scientists realised that DNA
contained the code for life, and in 1953 Watson and Crick at Cambridge
University discovered how information was stored in DNA and transferred to
the next generation.

In 1984 Professor Alec Jeffreys discovered
the variations in DNA, unique to each individual.

They are the same in every cell and retain
their distinctiveness throughout a person’s life.

Human cells contain 23 chromosomes (packets
of DNA) from the father and 23 from the mother.

Each DNA strand contains a unique sequence
or code of genetic information. But while most of DNA shows only slight
variation from one person to the next, certain areas, called 'minisatellites'
(short sequences of chemical building blocks) show variation in the
numbers of repeat units (or stutters) unique to each person.

DNA information can be recovered from human
and animal remains as far back as Neanderthal man, and has been used to
solve a number of high profile mysteries from the past, including the
identification of Josef Mengele’s skeleton and the identity of children
of US President Thomas Jefferson’s children by one of his slaves.

Apart from identification, paternity and
immigration cases, the technique is also used in medical research
including cancer and genetic conditions such as Huntingtons disease.

GENETIC FINGERPRINTING INVOLVES:

the extraction of DNA,

using enzymes to cut it into fragments some
of which will contain minisatellites

separating the fragments according to size

treating the fragments with a radioactive
probe which identifies shared motifs and can be captured on X-ray film

the result will be a pattern of more than 30
stripes, resembling a 'bar code'

GENETIC PROFILING

This involves testing minisatellites one at a
time, producing a simpler image than genetic fingerprinting.

It gives a pattern unique to a particular
person, and is therefore suitable for forensic cases.

In the words of Professor Sir Alec Jeffreys,
“It does not solve crimes. It establishes whether sample X comes from
person Y. It is then up to the court to interpret that in the context of
other evidence in a criminal case.”